Adjuvant chemotherapy (CTh) is an established postoperative treatment often prescribed to cancer patients to reduce risk of relapse. However, a great proportion of patients report experiencing cognitive, psychomotor, and other functional impairments associated with CTh. Some symptoms may persist for years after treatment and can have dramatic consequences on cancer survivors' quality of life. Despite numerous studies reporting various symptoms during/after CTh treatment, mechanisms underlying these symptoms are not well understood. Recent animal and human brain imaging studies suggest that CTh may have direct neurotoxic effects on the brain, in particular on brain white matter (WM). However, to date, no longitudinal studies have been done to examine the effects of CTh on cortical/subcortical WM integrity in human patients. Furthermore, no effort has yet been made to correlate a given WM structure with its corresponding neurophysiological function (NPF) and behavior. This study proposes longitudinal experiments in women diagnosed with breast cancer to examine the effects of CTh on the corpus callosum (CC) and corticospinal tract (CST) (Aim 1), on NPF that directly depends on the quality of CC/CST structure, and on psychomotor behavior critically relying on CC/CST function (conductivity) (Aim 2). The relationship between CC/CST structural integrity and their corresponding NPF and psychomotor behavior will also be examined (Aim 3). The general underlying hypotheses of the study are that (1) CTh has a direct neurotoxic effect on the CC and CST, resulting in microstructural degeneration and (2) structural damage to the CC and CST impairs relevant neurophysiological function and behavior. This research is expected to yield significant information regarding neural structural and physiological causes of CTh-related side effects; known this information would help more effectively manage the symptoms. By demonstrating direct evidence of detrimental consequences of CTh on the central nervous system, it is hoped that the evidence would encourage pharmaceutical companies to develop safer cancer treatment drugs. PUBLIC HEALTH RELEVANCE: A majority of cancer survivors suffer chemotherapy side effects, including cognitive and psychomotor function impairment that diminishes their quality of life. The goal of this research is to investigate how currently widely used chemotherapy drugs affect structure and function of brain nerve fibers and relevant psychomotor behavior. The findings are expected to help uncover the cause of cancer treatment side effects and better manage them and facilitate development of safer cancer treatment drugs by showing harmful effects of chemotherapy on the nervous system.